S115: CONSOLIDATION WITH BLINATUMOMAB IMPROVES OVERALL AND RELAPSE-FREE SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: IMPACT OF AGE AND MRD LEVEL IN ECOG-ACRIN E1910
Notice bibliographique
Résumé
Background: Patients (pts) with newly diagnosed acute lymphoblastic leukemia (ALL) often relapse even with achieving complete remission (CR) and minimal residual disease (MRD) negative (MRD-) status after chemotherapy (chemo). Blinatumomab (blin) is a bi-specific T cell engager molecule approved for relapsed/refractory ALL pts and pts MRD positive (MRD+) (>0.1%) in 1st or 2nd CR. E1910 was a phase III trial randomizing pts age 30-70 yrs to chemo +/-blin to test whether blin improves outcomes in BCR:ABL-negative B-ALL. The study showed that in pts who were MRD- after induction, there was a significant improvement in overall survival (OS) in favor of the blin arm. These subgroup analyses describe outcomes in pts based on age (< or > 55 yr) and depth of MRD (undetectable vs between undetectable-0.01%). Aims: Primary objective compared OS in MRD- pts who received chemo +/- blin. Subgroup analyses look at outcomes based on age <55 or >=55 yrs, which was a pre-specified stratification factor. Additional subgroup analyses look at depth of MRD below 0.01%, which was not a pre-specified stratification factor. Methods: Pts received 2.5 mo of combination chemo using a BFM-like regimen adapted from the E2993/UKALLXII clinical trial with extended remission induction, addition of pegaspargase for pts <55 yr of age and addition of rituximab for CD20+ pts. Details regarding remission induction (step 1), high dose methotrexate with pegaspargase for CNS prophylaxis (step 2), blin randomization (step 3), and maintenance (step 4) or hematopoietic cell transplant (HCT) were presented previously at ASH 2022. MRD status was determined centrally by 6-color flow cytometry with level of sensitivity of 0.01%. MRD- was defined as <0.01%. With a minimum of 190 MRD- pts, the study had an 80% power to detect a 45% reduction in hazard rate in the blin arm relative to the control chemo arm, using one-sided log rank test at significance level of 0.025 and assuming 2 yrs of follow-up. Estimates of OS were calculated using the Kaplan-Meier method. Comparison of OS between treatment arms was conducted using age, CD20 status, rituximab use, and whether pts were intended to receive HCT or not as stratification factors. Results: 772 pts were screened and 488 were enrolled. Median age was 51 yr. 224 MRD- pts were randomized, 112 pts to each arm. 22 pts in each arm proceeded to allogeneic HCT. The CR/CRi rate after induction was 81%. Among MRD- pts, OS significantly favored the blin arm (median OS: not reached vs. 71.4 mo; Hazard ratio (HR) 0.42, 95% CI: 0.24 - 0.75; two-sided p=0.003). The RFS in MRD- pts (n=224) favored the blin arm (median RFS: not reached vs. 71.4 mo; HR 0.46, 95% CI:.027-0.78; p=0.004). In MRD+ pts (N=62), the OS for blin vs control arm was (median OS: not reached vs 22.4 months; HR 0.39, 95% CI: 0.14-1.10; p=0.066). In MRD- pts < 55 yr (n=132), OS favored the blin arm (median OS not reached vs not reached; HR 0.18, 95% CI: 0.06-0.52; p <0.001). In MRD- pts >55 yr (n=92), the OS for blin vs control arm was (median OS not reached vs. 71.4 mo; HR 0.77, 95% CI: 0.37-1.58; p=0.47). In pts with undetectable MRD (n=187) at randomization, OS favored the blin arm (median OS not reached vs. not reached; HR 0.51, 95% CI: 0.27-0.97; p=0.038). In pts with MRD between undetectable and 0.01% (n=37), the OS for blin vs control arm was (median OS not reached vs. 38.0 mo; HR 0.35, 95% CI 0.06-1.94; p=0.16). Summary/Conclusion: Adding blin to chemo improves OS and RFS in pts MRD- at randomization. The effect of blin was particularly evident in pts < 55 yr and in patients with undetectable MRD. Keywords: B cell acute lymphoblastic leukemia, Acute lymphoblastic leukemia, Immunotherapy
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».